Clara cell secretory protein (CC16) as a peripheral blood biomarker of lung injury in ventilated preterm neonates

Abstract

The aim of this study was to assess the serum concentrations of Clara cell secretory protein (CC16) in association with acute and chronic lung injury in mechanically ventilated preterm neonates. Thirty-five preterm neonates (gestational age [GA] <or=31 weeks) with acute respiratory failure were enrolled. Of these, 23 neonates requiring ventilatory support within 2 h after birth comprised the mechanically ventilated group (MV group), and 12 neonates who were not ventilated made up the nonventilated group (NV group). Serum CC16 was measured (using enzyme-linked immunosorbent assay [ELISA]) within 2 h (T0) and at 72 h (T1) after birth, at day 14 of life (T2) and at 36 weeks postmenstrual age (T3). The median CC16 concentrations were significantly higher in the MV group compared to the NV group at all times. Analysis with respect to differences observed in the group characteristics showed that GA, Apgar score at 5 min and mechanical ventilation were significant covariates of serum CC16 at T0. All neonates in the NV group and 18 cases in the MV group, respectively, survived discharge. Ventilated survivors with later bronchopulmonary dysplasia (BPD; oxygen requirement at T3, n = 7) had significantly higher CC16 at all times compared to nonventilated neonates. Elevated serum CC16 levels at T2 were predictive of BPD development. In conclusion, our results show that serum CC16 increases significantly in preterm neonates ventilated early after birth and remains high in those with later BPD. Further research is needed to validate the usefulness of CC16 as a peripheral blood biomarker of acute and chronic lung injury.

Comparable effect of conventional ventilation versus early high-frequency oscillation on serum CC16 and IL-6 levels in preterm neonates

“…Serum CC16 and IL-6 in preterm neonates K Sarafidis et al Disruption of the alveolar membrane with mechanical ventilation enhances leakage of CC16 from the alveoli into the bloodstream as documented in experimental models of acute lung injury, 21 adults ventilated for acute respiratory failure 9,11 and preterm neonates with RDS. 14 Nevertheless, although all types of mechanical ventilation cause structural disruption of the alveoli, 22 damage of the alveolar-capillary barrier and protein leakage was found to be less with HFOV, at least in animal studies. 23 This was not confirmed in this clinical study rejecting our initial hypothesis, because SIMV and HFOV were associated with comparable CC16 levels in the bloodstream.…”

“…14 Similarly, Loughran-Fowlds et al 13 reported increased serum CC16 in mechanically ventilated preterm neonates, speculating that high blood concentrations of the specific protein at birth may represent a protective mechanism during acute postnatal lung adaptation. CC16 is a protein with favorable action against hyperoxic injury, surfactant degradation and inflammation of the lung.…”

“…7,8 Recently, Clara cell protein (CC16) has been used as peripheral blood biomarker of various lung diseases in adults, [9][10][11] children 12 and neonates. 13,14 CC16 is a lung-specific protein produced by the tracheobronchial epithelium, especially in the terminal bronchioles in which nonciliated Clara cells are localized and is believed to raise in the blood stream of subjects with pathological situations characterized by increased permeability of the alveolar-capillary barrier. 15 On this basis, we advanced the hypothesis that measurement of CC16 in the peripheral blood could detect changes of the alveolar integrity occurring with different ventilatory modes (HFOV vs pressure synchronized intermittent mandatory ventilation (SIMV)).…”

Early Effect of Tidal Volume on Lung Injury Biomarkers in Surgical Patients With Healthy Lungs

“…CC16 is a small protein secreted by epithelial Clara cells and an accepted biomarker of alveolar-capillary permeability 34 . Leakage of CC16 into the circulation is observed after lipopolysaccharide inhalation in healthy humans 71 , lung contusion 72 and mechanical ventilation in preterm neonates 36 or animal models 73 . Plasma CC16 concentrations are increased in ventilated ARDS patients 58 and predict poor outcomes such as greater mortality and fewer ventilator-free days 35 .…”

“…The plasma concentration of neutrophil elastase (NE) is an indicator of alveolar recruitment 32 and activation of neutrophils during the development of lung injury 33 . Finally, plasma Clara cell protein 16 (CC16), an antiinflammatory protein secreted by the Clara cells of the distal respiratory epithelium, is a marker of acute epithelial lung injury 34,35 and increases in ventilated preterm neonates 36 and after 5-h ventilation during abdominal surgery in adults 37 .…”